1 264 118 ADVANCING ASTHMA CARE: THE GLASS IS ONLY HALF FULL! OVER THE PAST 20 YEARS, THERE HAS BEEN A CONCERTED EFFORT IN THE UNITED STATES TO REDUCE MORBIDITY RELATED TO CHRONIC DISEASE, INCLUDING ASTHMA. ATTENTION WAS INITIALLY DIRECTED TOWARD ASTHMA IN RESPONSE TO THE RECOGNITION THAT ASTHMA MORTALITY WAS INCREASING AND THAT THE BURDEN OF DISEASE WAS SIGNIFICANT. THESE EFFORTS TO ADDRESS ASTHMA MORTALITY LED TO MANY NEW INITIATIVES TO DEVELOP CLINICAL PRACTICE GUIDELINES, IMPLEMENT THE ASTHMA GUIDELINES INTO CLINICAL PRACTICE, CONDUCT RESEARCH TO FILL THE GAPS IN THE GUIDELINES, AND CONTINUOUSLY REVISE THE ASTHMA GUIDELINES AS MORE INFORMATION BECAME AVAILABLE. AN ASSESSMENT OF OUR PROGRESS SHOWS SIGNIFICANT ACCOMPLISHMENTS IN RELATION TO REDUCING ASTHMA MORTALITY AND HOSPITALIZATIONS. CONSEQUENTLY, WE ARE NOW AT A CROSSROADS IN ASTHMA CARE. ALTHOUGH WE HAVE RECOGNIZED SOME REMARKABLE ACCOMPLISHMENTS IN REDUCING ASTHMA MORTALITY AND MORBIDITY, THE AVAILABILITY OF NEW TOOLS TO MONITOR DISEASE ACTIVITY, INCLUDING BIOMARKERS AND EPIGENETIC MARKERS, ALONG WITH INFORMATION TECHNOLOGY SYSTEMS TO MONITOR ASTHMA CONTROL HOLD SOME PROMISE IN IDENTIFYING GAPS IN DISEASE MANAGEMENT. THESE ADVANCES SHOULD PROMPT THE EVOLUTION OF NEW STRATEGIES AND NEW TREATMENTS TO FURTHER REDUCE DISEASE BURDEN. IT NOW BECOMES IMPERATIVE TO CONTINUE A FOCUS ON WAYS TO FURTHER REDUCE THE BURDEN OF ASTHMA AND PREVENT ITS ONSET. 2011 2 1388 20 DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE: NON-INVASIVE ASSESSMENT OF CARDIOVASCULAR RISK. THE PREVALENCE AND BURDEN OF DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE ON GLOBAL HEALTH AND SOCIOECONOMIC DEVELOPMENT IS ALREADY HEAVY AND STILL RISING. DIABETES MELLITUS BY ITSELF IS LINKED TO ADVERSE CARDIOVASCULAR EVENTS, AND THE PRESENCE OF CONCOMITANT CHRONIC KIDNEY DISEASE FURTHER AMPLIFIES CARDIOVASCULAR RISK. THE CULMINATION OF TRADITIONAL (MALE GENDER, SMOKING, ADVANCED AGE, OBESITY, ARTERIAL HYPERTENSION AND DYSLIPIDEMIA) AND NON-TRADITIONAL RISK FACTORS (ANEMIA, INFLAMMATION, PROTEINURIA, VOLUME OVERLOAD, MINERAL METABOLISM ABNORMALITIES, OXIDATIVE STRESS, ETC.) CONTRIBUTES TO ADVANCED ATHEROSCLEROSIS AND INCREASED CARDIOVASCULAR RISK. TO DECREASE THE MORBIDITY AND MORTALITY OF THESE PATIENTS DUE TO CARDIOVASCULAR CAUSES, TIMELY AND EFFICIENT CARDIOVASCULAR RISK ASSESSMENT IS OF HUGE IMPORTANCE. CARDIOVASCULAR RISK ASSESSMENT CAN BE BASED ON LABORATORY PARAMETERS, IMAGING TECHNIQUES, ARTERIAL STIFFNESS PARAMETERS, ANKLE-BRACHIAL INDEX AND 24 H BLOOD PRESSURE MEASUREMENTS. NEWER METHODS INCLUDE EPIGENETIC MARKERS, SOLUBLE ADHESION MOLECULES, CYTOKINES AND MARKERS OF OXIDATIVE STRESS. IN THIS REVIEW, THE AUTHORS PRESENT SEVERAL NON-INVASIVE METHODS OF CARDIOVASCULAR RISK ASSESSMENT IN PATIENTS WITH DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE. 2021 3 5175 29 PREDICTORS OF BIOLOGICAL AGE: THE IMPLICATIONS FOR WELLNESS AND AGING RESEARCH. AS HEALTHSPAN AND LIFESPAN RESEARCH BREAKTHROUGHS HAVE BECOME MORE COMMONPLACE, THE NEED FOR VALID, PRACTICAL MARKERS OF BIOLOGICAL AGE IS BECOMING INCREASINGLY PARAMOUNT. THE ACCESSIBILITY AND AFFORDABILITY OF BIOLOGICAL AGE PREDICTORS THAT CAN REVEAL INFORMATION ABOUT MORTALITY AND MORBIDITY RISK, AS WELL AS REMAINING YEARS OF LIFE, HAS PROFOUND CLINICAL AND RESEARCH IMPLICATIONS. IN THIS REVIEW, WE EXAMINE 5 GROUPS OF AGING BIOMARKERS CAPABLE OF PROVIDING ACCURATE BIOLOGICAL AGE ESTIMATIONS. THE UNIQUE CAPABILITIES OF THESE BIOMARKERS HAVE FAR REACHING IMPLICATIONS FOR THE TESTING OF BOTH PHARMACEUTICAL AND NON-PHARMACEUTICAL INTERVENTIONS DESIGNED TO SLOW OR REVERSE BIOLOGICAL AGING. ADDITIONALLY, THE ENHANCED VALIDITY AND AVAILABILITY OF THESE TOOLS MAY HAVE INCREASINGLY RELEVANT CLINICAL VALUE. THE AUTHORS OF THIS REVIEW EXPLORE THOSE IMPLICATIONS, WITH AN EMPHASIS ON LIFESTYLE MODIFICATION RESEARCH, AND PROVIDE AN OVERVIEW OF THE CURRENT EVIDENCE REGARDING 5 BIOLOGICAL AGE PREDICTOR CATEGORIES: TELOMERE LENGTH, COMPOSITE BIOMARKERS, DNA METHYLATION "EPIGENETIC CLOCKS," TRANSCRIPTIONAL PREDICTORS OF BIOLOGICAL AGE, AND FUNCTIONAL AGE PREDICTORS. 2021 4 929 22 CHRONIC INFLAMMATION: ACCELERATOR OF BIOLOGICAL AGING. BIOLOGICAL AGING IS CHARACTERIZED BY A CHRONIC LOW-GRADE INFLAMMATION LEVEL. THIS CHRONIC PHENOMENON HAS BEEN NAMED "INFLAMM-AGING" AND IS A HIGHLY SIGNIFICANT RISK FACTOR FOR MORBIDITY AND MORTALITY IN THE OLDER PERSONS. THE MOST COMMON THEORIES OF INFLAMM-AGING INCLUDE REDOX STRESS, MITOCHONDRIAL DYSFUNCTION, GLYCATION, DEREGULATION OF THE IMMUNE SYSTEM, HORMONAL CHANGES, EPIGENETIC MODIFICATIONS, AND DYSFUNCTION TELOMERE ATTRITION. INFLAMM-AGING PLAYS A ROLE IN THE INITIATION AND PROGRESSION OF AGE-RELATED DISEASES SUCH AS TYPE II DIABETES, ALZHEIMER'S DISEASE, CARDIOVASCULAR DISEASE, FRAILTY, SARCOPENIA, OSTEOPOROSIS, AND CANCER. THIS REVIEW WILL COVER THE IDENTIFICATION OF PATHWAYS THAT CONTROL AGE-RELATED INFLAMMATION ACROSS MULTIPLE SYSTEMS AND ITS POTENTIAL CAUSAL ROLE IN CONTRIBUTING TO ADVERSE HEALTH OUTCOMES. 2017 5 5224 39 PRIORITIZED RESEARCH FOR THE PREVENTION, TREATMENT, AND REVERSAL OF CHRONIC DISEASE: RECOMMENDATIONS FROM THE LIFESTYLE MEDICINE RESEARCH SUMMIT. DECLINING LIFE EXPECTANCY AND INCREASING ALL-CAUSE MORTALITY IN THE UNITED STATES HAVE BEEN ASSOCIATED WITH UNHEALTHY BEHAVIORS, SOCIOECOLOGICAL FACTORS, AND PREVENTABLE DISEASE. A GROWING BODY OF BASIC SCIENCE, CLINICAL RESEARCH, AND POPULATION HEALTH EVIDENCE POINTS TO THE BENEFITS OF HEALTHY BEHAVIORS, ENVIRONMENTS AND POLICIES TO MAINTAIN HEALTH AND PREVENT, TREAT, AND REVERSE THE ROOT CAUSES OF COMMON CHRONIC DISEASES. SIMILARLY, INNOVATIONS IN RESEARCH METHODOLOGIES, STANDARDS OF EVIDENCE, EMERGENCE OF UNIQUE STUDY COHORTS, AND BREAKTHROUGHS IN DATA ANALYTICS AND MODELING CREATE NEW POSSIBILITIES FOR PRODUCING BIOMEDICAL KNOWLEDGE AND CLINICAL TRANSLATION. TO UNDERSTAND THESE ADVANCES AND INFORM FUTURE DIRECTIONS RESEARCH, THE LIFESTYLE MEDICINE RESEARCH SUMMIT WAS CONVENED AT THE UNIVERSITY OF PITTSBURGH ON DECEMBER 4-5, 2019. THE SUMMIT'S GOAL WAS TO REVIEW CURRENT STATUS AND DEFINE RESEARCH PRIORITIES IN THE SIX CORE AREAS OF LIFESTYLE MEDICINE: PLANT-PREDOMINANT NUTRITION, PHYSICAL ACTIVITY, SLEEP, STRESS, ADDICTIVE BEHAVIORS, AND POSITIVE PSYCHOLOGY/SOCIAL CONNECTION. FORTY INVITED SUBJECT MATTER EXPERTS (1) REVIEWED EXISTING KNOWLEDGE AND GAPS RELATING LIFESTYLE BEHAVIORS TO COMMON CHRONIC DISEASES, SUCH AS CARDIOVASCULAR DISEASE, DIABETES, MANY CANCERS, INFLAMMATORY- AND IMMUNE-RELATED DISORDERS AND OTHER CONDITIONS; AND (2) DISCUSSED THE POTENTIAL FOR APPLYING CUTTING-EDGE MOLECULAR, CELLULAR, EPIGENETIC AND EMERGING SCIENCE KNOWLEDGE AND COMPUTATIONAL METHODOLOGIES, RESEARCH DESIGNS, AND STUDY COHORTS TO ACCELERATE CLINICAL APPLICATIONS ACROSS ALL SIX DOMAINS OF LIFESTYLE MEDICINE. NOTABLY, FEDERAL HEALTH AGENCIES, SUCH AS THE DEPARTMENT OF DEFENSE AND VETERANS ADMINISTRATION HAVE BEGUN TO ADOPT "WHOLE-PERSON HEALTH AND PERFORMANCE" MODELS THAT ADDRESS THESE LIFESTYLE AND ENVIRONMENTAL ROOT CAUSES OF CHRONIC DISEASE AND ASSOCIATED MORBIDITY, MORTALITY, AND COST. RECOMMENDATIONS STRONGLY SUPPORT LEVERAGING EMERGING RESEARCH METHODOLOGIES, SYSTEMS BIOLOGY, AND COMPUTATIONAL MODELING IN ORDER TO ACCELERATE EFFECTIVE CLINICAL AND POPULATION SOLUTIONS TO IMPROVE HEALTH AND REDUCE SOCIETAL COSTS. NEW AND ALTERNATIVE HIERARCHIES OF EVIDENCE ARE ALSO BE NEEDED IN ORDER TO ASSESS THE QUALITY OF EVIDENCE AND DEVELOP EVIDENCE-BASED GUIDELINES ON LIFESTYLE MEDICINE. CHILDREN AND UNDERSERVED POPULATIONS WERE IDENTIFIED AS PRIORITIZED GROUPS TO STUDY. THE COVID-19 PANDEMIC, WHICH DISPROPORTIONATELY IMPACTS PEOPLE WITH CHRONIC DISEASES THAT ARE AMENABLE TO EFFECTIVE LIFESTYLE MEDICINE INTERVENTIONS, MAKES THE SUMMIT'S FINDINGS AND RECOMMENDATIONS FOR FUTURE RESEARCH PARTICULARLY TIMELY AND RELEVANT. 2020 6 529 18 ASTHMA IN URBAN CHILDREN: EPIDEMIOLOGY, ENVIRONMENTAL RISK FACTORS, AND THE PUBLIC HEALTH DOMAIN. ASTHMA IS THE MOST COMMONLY REPORTED CHRONIC CONDITION OF CHILDHOOD IN DEVELOPED COUNTRIES, WITH 6.5 MILLION CHILDREN AFFECTED IN THE USA. A DISPARATE BURDEN OF CHILDHOOD ASTHMA IS SEEN AMONG SOCIOECONOMICALLY DISADVANTAGED YOUTH, OFTEN CONCENTRATED IN URBAN AREAS WITH HIGH POVERTY RATES. HOST FACTORS THAT PREDISPOSE A CHILD TO ASTHMA INCLUDE ATOPY, MALE GENDER, PARENTAL HISTORY OF ASTHMA, AND ALSO RACE, ETHNICITY, AND GENETIC AND EPIGENETIC SUSCEPTIBILITIES. ENVIRONMENTAL FACTORS, SUCH AS IMPROVED HYGIENE, AMBIENT AIR POLLUTION, AND EARLY LIFE EXPOSURES TO MICROBES AND AEROALLERGENS, ALSO INFLUENCE THE DEVELOPMENT OF ASTHMA. WITH GREATER THAN 90% OF TIME SPENT INDOORS, HOME EXPOSURES (SUCH AS COCKROACH, RODENT, AND INDOOR AIR POLLUTION) ARE HIGHLY RELEVANT FOR URBAN ASTHMA. MORBIDITY REDUCTION MAY REQUIRE FOCUSED PUBLIC HEALTH INITIATIVES FOR ENVIRONMENTAL INTERVENTION IN HIGH PRIORITY RISK GROUPS AND THE ADDITION OF IMMUNE MODULATORY AGENTS IN CHILDREN WITH POORLY CONTROLLED DISEASE. 2016 7 1883 31 END-STAGE RENAL DISEASE, INFLAMMATION AND CARDIOVASCULAR OUTCOMES. DESPITE MARKED IMPROVEMENTS IN RENAL REPLACEMENT THERAPY DURING THE LAST 30 YEARS, THE AGE-ADJUSTED MORTALITY RATE IN END-STAGE RENAL DISEASE (ESRD) PATIENTS IS STILL UNACCEPTABLY HIGH AND COMPARABLE TO THAT OF MANY MALIGNANCIES. CARDIOVASCULAR DISEASE (CVD) REMAINS THE MAJOR CAUSE OF MORBIDITY AND MORTALITY IN ESRD PATIENTS. HOWEVER, TRADITIONAL RISK FACTORS CAN ONLY PARTIALLY EXPLAIN THE HIGH PREMATURE CARDIOVASCULAR BURDEN IN THIS POPULATION. NONTRADITIONAL RISK FACTORS, INCLUDING PERSISTENT LOW-GRADE INFLAMMATION, ARE CRITICAL IN THE PATHOGENESIS OF ATHEROSCLEROSIS, VASCULAR CALCIFICATION, AND OTHER CAUSES OF CVD AND MAY ALSO CONTRIBUTE TO PROTEIN-ENERGY WASTING AND OTHER COMPLICATIONS IN CHRONIC KIDNEY DISEASE (CKD) PATIENTS. INFLAMMATORY BIOMARKERS, SUCH AS HIGH SENSITIVITY C-REACTIVE PROTEIN AND INTERLEUKIN-6, INDEPENDENTLY PREDICT MORTALITY IN THESE PATIENTS. THE CAUSES OF INFLAMMATION IN CKD ARE MULTIFACTORIAL AND INCLUDE IMBALANCE BETWEEN INCREASED PRODUCTION (DUE TO MULTIPLE SOURCES OF INFLAMMATORY STIMULI SUCH AS OXIDATIVE STRESS, ACIDOSIS, VOLUME OVERLOAD, CO-MORBIDITIES, ESPECIALLY INFECTIONS, GENETIC AND EPIGENETIC INFLUENCES, AND THE DIALYSIS PROCEDURE) AND INADEQUATE REMOVAL (DUE TO DECREASED GLOMERULAR FILTRATION RATE OR IN ESRD PATIENTS, INADEQUATE DIALYTIC CLEARANCE) OF PRO-INFLAMMATORY CYTOKINES. THOUGH THERE ARE CURRENTLY NO ESTABLISHED GUIDELINES FOR THE TREATMENT OF LOW-GRADE INFLAMMATION IN ESRD PATIENTS, SEVERAL STRATEGIES HAVE BEEN PROPOSED, SUCH AS LIFESTYLE MODIFICATIONS, PHARMACOLOGICAL TREATMENT, AND OPTIMIZATION OF DIALYSIS. FURTHER STUDIES ON PATHWAYS INVOLVED IN PATHOGENIC PROCESSES OF INFLAMMATION IN ESRD, AND LONG-TERM EFFECTS OF ANTI-INFLAMMATORY INTERVENTIONS TARGETING PRODUCTION OR REMOVAL OF CYTOKINES OR BOTH ON PREMATURE CVD AND CLINICAL OUTCOMES IN THIS PATIENT GROUP ARE WARRANTED. 2017 8 5161 39 PRECISION AND PERSONALIZED MEDICINE: HOW GENOMIC APPROACH IMPROVES THE MANAGEMENT OF CARDIOVASCULAR AND NEURODEGENERATIVE DISEASE. LIFE EXPECTANCY HAS GRADUALLY GROWN OVER THE LAST CENTURY. THIS HAS DEEPLY AFFECTED HEALTHCARE COSTS, SINCE THE GROWTH OF AN AGING POPULATION IS CORRELATED TO THE INCREASING BURDEN OF CHRONIC DISEASES. THIS REPRESENTS THE INTERESTING CHALLENGE OF HOW TO MANAGE PATIENTS WITH CHRONIC DISEASES IN ORDER TO IMPROVE HEALTH CARE BUDGETS. EFFECTIVE PRIMARY PREVENTION COULD REPRESENT A PROMISING ROUTE. TO THIS END, PRECISION, TOGETHER WITH PERSONALIZED MEDICINE, ARE USEFUL INSTRUMENTS IN ORDER TO INVESTIGATE PATHOLOGICAL PROCESSES BEFORE THE APPEARANCE OF CLINICAL SYMPTOMS AND TO GUIDE PHYSICIANS TO CHOOSE A TARGETED THERAPY TO MANAGE THE PATIENT. CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES REPRESENT SUITABLE MODELS FOR TAKING FULL ADVANTAGE OF PRECISION MEDICINE TECHNOLOGIES APPLIED TO ALL STAGES OF DISEASE DEVELOPMENT. THE AVAILABILITY OF HIGH TECHNOLOGY INCORPORATING ARTIFICIAL INTELLIGENCE AND ADVANCEMENT PROGRESS MADE IN THE FIELD OF BIOMEDICAL RESEARCH HAVE BEEN SUBSTANTIAL TO UNDERSTAND HOW GENES, EPIGENETIC MODIFICATIONS, AGING, NUTRITION, DRUGS, MICROBIOME AND OTHER ENVIRONMENTAL FACTORS CAN IMPACT HEALTH AND CHRONIC DISORDERS. THE AIM OF THE PRESENT REVIEW IS TO ADDRESS HOW PRECISION AND PERSONALIZED MEDICINE CAN BRING GREATER CLARITY TO THE CLINICAL AND BIOLOGICAL COMPLEXITY OF THESE TYPES OF DISORDERS ASSOCIATED WITH HIGH MORTALITY, INVOLVING TREMENDOUS HEALTH CARE COSTS, BY DESCRIBING IN DETAIL THE METHODS THAT CAN BE APPLIED. THIS MIGHT OFFER PRECIOUS TOOLS FOR PREVENTIVE STRATEGIES AND POSSIBLE CLUES ON THE EVOLUTION OF THE DISEASE AND COULD HELP IN PREDICTING MORBIDITY, MORTALITY AND DETECTING CHRONIC DISEASE INDICATORS MUCH EARLIER IN THE DISEASE COURSE. THIS, OF COURSE, WILL HAVE A MAJOR EFFECT ON BOTH IMPROVING THE QUALITY OF CARE AND QUALITY OF LIFE OF THE PATIENTS AND REDUCING TIME EFFORTS AND HEALTHCARE COSTS. 2020 9 2605 22 EPIGENETICS-A POTENTIAL MEDIATOR BETWEEN AIR POLLUTION AND PRETERM BIRTH. PRETERM BIRTH IS A MAJOR CAUSE OF INFANT MORBIDITY AND MORTALITY AND A POTENTIAL RISK FACTOR FOR ADULT CHRONIC DISEASE. WITH OVER 15 MILLION INFANTS BORN PRETERM WORLDWIDE EACH YEAR, PRETERM BIRTH POSES A GLOBAL HEALTH CONCERN. THERE IS A POSSIBLE ASSOCIATION BETWEEN AIR POLLUTION AND PRETERM BIRTH, THOUGH STUDIES HAVE BEEN INCONSISTENT, LIKELY DUE TO VARIATION IN STUDY DESIGN. HOW AIR POLLUTION INDUCES HEALTH EFFECTS IS UNCERTAIN; HOWEVER, STUDIES HAVE REPEATEDLY DEMONSTRATED THE EFFECTS OF AIR POLLUTION ON EPIGENETIC MODIFICATIONS. MORE RECENT EVIDENCE SUGGESTS THAT EPIGENETICS MAY, IN TURN, BE LINKED TO PRETERM BIRTH. DISCOVERY OF ENVIRONMENTALLY MODIFIABLE EPIGENETIC PROCESSES CONNECTED TO PRETERM BIRTH MAY HELP TO IDENTIFY WOMEN AT RISK OF PRETERM BIRTH, AND ULTIMATELY LEAD TO DEVELOPMENT OF NEW PRETERM BIRTH PREVENTION MEASURES. 2016 10 6652 32 UPDATE ON INFLAMMATION IN CHRONIC KIDNEY DISEASE. BACKGROUND: DESPITE RECENT ADVANCES IN CHRONIC KIDNEY DISEASE (CKD) AND END-STAGE RENAL DISEASE (ESRD) MANAGEMENT, MORBIDITY AND MORTALITY IN THIS POPULATION REMAIN EXCEPTIONALLY HIGH. PERSISTENT, LOW-GRADE INFLAMMATION HAS BEEN RECOGNIZED AS AN IMPORTANT COMPONENT OF CKD, PLAYING A UNIQUE ROLE IN ITS PATHOPHYSIOLOGY AND BEING ACCOUNTABLE IN PART FOR CARDIOVASCULAR AND ALL-CAUSE MORTALITY, AS WELL AS CONTRIBUTING TO THE DEVELOPMENT OF PROTEIN-ENERGY WASTING. SUMMARY: THE VARIETY OF FACTORS CONTRIBUTE TO CHRONIC INFLAMMATORY STATUS IN CKD, INCLUDING INCREASED PRODUCTION AND DECREASED CLEARANCE OF PRO-INFLAMMATORY CYTOKINES, OXIDATIVE STRESS AND ACIDOSIS, CHRONIC AND RECURRENT INFECTIONS, INCLUDING THOSE RELATED TO DIALYSIS ACCESS, ALTERED METABOLISM OF ADIPOSE TISSUE, AND INTESTINAL DYSBIOSIS. INFLAMMATION DIRECTLY CORRELATES WITH THE GLOMERULAR FILTRATION RATE (GFR) IN CKD AND CULMINATES IN DIALYSIS PATIENTS, WHERE EXTRACORPOREAL FACTORS, SUCH AS IMPURITIES IN DIALYSIS WATER, MICROBIOLOGICAL QUALITY OF THE DIALYSATE, AND BIOINCOMPATIBLE FACTORS IN THE DIALYSIS CIRCUIT PLAY AN ADDITIONAL ROLE. GENETIC AND EPIGENETIC INFLUENCES CONTRIBUTING TO INFLAMMATORY ACTIVATION IN CKD ARE CURRENTLY BEING INTENSIVELY INVESTIGATED. A NUMBER OF INTERVENTIONS HAVE BEEN PROPOSED TO TARGET INFLAMMATION IN CKD, INCLUDING LIFESTYLE MODIFICATIONS, PHARMACOLOGICAL AGENTS, AND OPTIMIZATION OF DIALYSIS. IMPORTANTLY, SOME OF THESE THERAPIES HAVE BEEN RECENTLY TESTED IN RANDOMIZED CONTROLLED TRIALS. KEY MESSAGES: CHRONIC INFLAMMATION SHOULD BE REGARDED AS A COMMON COMORBID CONDITION IN CKD AND ESPECIALLY IN DIALYSIS PATIENTS. A NUMBER OF INTERVENTIONS HAVE BEEN PROVEN TO BE SAFE AND EFFECTIVE IN WELL-DESIGNED CLINICAL STUDIES. THIS INCLUDES SUCH INEXPENSIVE APPROACHES AS MODIFICATION OF PHYSICAL ACTIVITY AND DIETARY SUPPLEMENTATION. FURTHER INVESTIGATIONS ARE NEEDED TO EVALUATE THE EFFECTS OF THESE INTERVENTIONS ON HARD OUTCOMES, AS WELL AS TO BETTER UNDERSTAND THE ROLE OF INFLAMMATION IN SELECTED CKD POPULATIONS (E.G., IN CHILDREN). 2015 11 1642 30 DOES INFLAMMATION AFFECT OUTCOMES IN DIALYSIS PATIENTS? CHRONIC, LOW-GRADE INFLAMMATION IS A COMMON COMORBID CONDITION IN CHRONIC KIDNEY DISEASE (CKD), AND PARTICULARLY IN CHRONIC DIALYSIS PATIENTS. IN THIS REVIEW, WE CONSIDER THE QUESTION OF WHETHER INFLAMMATION AFFECTS OUTCOMES IN DIALYSIS PATIENTS. LEVELS OF PROINFLAMMATORY CYTOKINES, AS WELL AS C-REACTIVE PROTEIN, ARE ELEVATED IN CHRONIC DIALYSIS PATIENTS. MULTIPLE FACTORS LIKELY CONTRIBUTE TO CHRONIC INFLAMMATORY ACTIVATION IN KIDNEY DISEASE PATIENTS INCLUDING THE UREMIC MILIEU, LIFESTYLE AND EPIGENETIC INFLUENCES, INFECTIOUS AND THROMBOTIC EVENTS, THE DIALYSIS PROCESS, AND DYSBIOSIS. INCREASED INFLAMMATORY MARKERS IN BOTH CKD AND CHRONIC DIALYSIS PATIENTS ARE ASSOCIATED WITH ADVERSE CLINICAL OUTCOMES INCLUDING ALL-CAUSE MORTALITY, CARDIOVASCULAR EVENTS, KIDNEY DISEASE PROGRESSION, PROTEIN ENERGY WASTING AND DIMINISHED MOTOR FUNCTION, COGNITIVE IMPAIRMENT, AS WELL AS OTHER ADVERSE CONSEQUENCES INCLUDING CKD-MINERAL AND BONE DISORDER, ANEMIA, AND INSULIN RESISTANCE. STRATEGIES THAT HAVE BEEN SHOWN TO REDUCE CHRONIC SYSTEMIC INFLAMMATION IN CKD AND CHRONIC DIALYSIS PATIENTS INCLUDE BOTH PHARMACOLOGICAL AND NONPHARMACOLOGICAL INTERVENTIONS. HOWEVER, DESPITE EVIDENCE THAT SYSTEMIC INFLAMMATORY MARKERS CAN BE LOWERED IN KIDNEY DISEASE PATIENTS TREATED WITH VARIOUS STRATEGIES, EVIDENCE THAT THIS IMPROVES CLINICAL OUTCOMES IS LARGELY UNAVAILABLE AND REPRESENTS AN IMPORTANT FUTURE RESEARCH DIRECTION. OVERALL, THERE IS STRONG OBSERVATIONAL EVIDENCE THAT INFLAMMATION IS HIGH IN CHRONIC DIALYSIS PATIENTS AND THAT THIS IS INDEPENDENTLY ASSOCIATED WITH NUMEROUS ADVERSE CLINICAL OUTCOMES. TARGETING INFLAMMATION REPRESENTS A POTENTIALLY NOVEL AND ATTRACTIVE STRATEGY IF IT CAN INDEED IMPROVE ADVERSE OUTCOMES COMMON IN THIS POPULATION. 2018 12 300 29 AIR POLLUTION AND INDOOR SETTINGS. INDOOR ENVIRONMENTS CONTRIBUTE SIGNIFICANTLY TO TOTAL HUMAN EXPOSURE TO AIR POLLUTANTS, AS PEOPLE SPEND MOST OF THEIR TIME INDOORS. HOUSEHOLD AIR POLLUTION (HAP) RESULTING FROM COOKING WITH POLLUTING ("DIRTY") FUELS, WHICH INCLUDE COAL, KEROSENE, AND BIOMASS (WOOD, CHARCOAL, CROP RESIDUES, AND ANIMAL MANURE) IS A GLOBAL ENVIRONMENTAL HEALTH PROBLEM. INDOOR POLLUTANTS ARE GASES, PARTICULATES, TOXINS, AND MICROORGANISMS AMONG OTHERS, THAT CAN HAVE AN IMPACT ESPECIALLY ON THE HEALTH OF CHILDREN AND ADULTS THROUGH A COMBINATION OF DIFFERENT MECHANISMS ON OXIDATIVE STRESS AND GENE ACTIVATION, EPIGENETIC, CELLULAR, AND IMMUNOLOGICAL SYSTEMS. AIR POLLUTION IS A MAJOR RISK FACTOR AND CONTRIBUTOR TO MORBIDITY AND MORTALITY FROM MAJOR CHRONIC DISEASES. CHILDREN ARE SIGNIFICANTLY AFFECTED BY THE IMPACT OF THE ENVIRONMENT DUE TO BIOLOGICAL IMMATURITY, PRENATAL AND POSTNATAL LUNG DEVELOPMENT. POOR AIR QUALITY HAS BEEN RELATED TO AN INCREASED PREVALENCE OF CLINICAL MANIFESTATIONS OF ALLERGIC ASTHMA AND RHINITIS. HEALTH PROFESSIONALS SHOULD INCREASE THEIR ROLE IN MANAGING THE EXPOSURE OF CHILDREN AND ADULTS TO AIR POLLUTION WITH BETTER METHODS OF CARE, PREVENTION, AND COLLECTIVE ACTION. INTERVENTIONS TO REDUCE HOUSEHOLD POLLUTANTS MAY PROMOTE HEALTH AND CAN BE ACHIEVED WITH EDUCATION, COMMUNITY, AND HEALTH PROFESSIONAL INVOLVEMENT. 2021 13 6123 28 THE EPIGENETIC MACHINERY IN VASCULAR DYSFUNCTION AND HYPERTENSION. HYPERTENSION (HT) IS AMONG THE MAJOR COMPONENTS OF THE METABOLIC SYNDROME, I.E., OBESITY, DYSLIPIDEMIA, AND HYPERGLYCEMIA/INSULIN RESISTANCE. IT REPRESENTS A SIGNIFICANT HEALTH PROBLEM WITH FOREMOST RISKS FOR CHRONIC CARDIOVASCULAR DISEASE AND A SIGNIFICANT CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE. THEREFORE, IT IS NOT SURPRISING THAT THIS DISORDER CONSTITUTES A SERIOUS PUBLIC HEALTH CONCERN. ALTHOUGH MULTIPLE STUDIES HAVE STRESSED THE MULTIFACTORIAL NATURE OF HT, THE PATHOGENESIS REMAINS LARGELY UNKNOWN. HOWEVER, IF WE WANT TO REDUCE THE GLOBAL PREVALENCE OF HT, RESTRAIN THE NUMBER OF DEATHS (CURRENTLY 9.4 MILLION/YEAR IN THE WORLD), AND ALLEVIATE THE SOCIO-ECONOMIC BURDEN, A DEEPER INSIGHT INTO THE MECHANISMS IS URGENTLY NEEDED IN ORDER TO DEFINE NEW MEANINGFUL THERAPEUTIC TARGETS. RECENTLY, THE ROLE OF EPIGENETICS IN THE DEVELOPMENT OF VARIOUS COMPLEX DISEASES HAS ATTRACTED MUCH ATTENTION. IN THE PRESENT REVIEW, WE PROVIDE A CRITICAL UPDATE ON THE AVAILABLE LITERATURE AND ONGOING RESEARCH REGARDING THE EPIGENETIC MODIFICATIONS OF GENES INVOLVED IN SEVERAL PATHWAYS OF ELEVATED BLOOD PRESSURE, ESPECIALLY THOSE LINKED TO THE VASCULAR EPITHELIUM. THIS REVIEW ALSO FOCUSES ON THE ROLE OF MICRORNA (MIRNA) IN THE REGULATION OF GENE EXPRESSION ASSOCIATED WITH HT AND OF FETAL PROGRAMMING MEDIATING SUSCEPTIBILITY TO HT IN ADULTHOOD. 2017 14 4467 20 MOLECULAR MECHANISMS OF VASCULAR HEALTH: INSIGHTS FROM VASCULAR AGING AND CALCIFICATION. CARDIOVASCULAR DISEASE IS THE MOST COMMON CAUSE OF DEATH WORLDWIDE, ESPECIALLY BEYOND THE AGE OF 65 YEARS, WITH THE VAST MAJORITY OF MORBIDITY AND MORTALITY DUE TO MYOCARDIAL INFARCTION AND STROKE. VASCULAR PATHOLOGY STEMS FROM A COMBINATION OF GENETIC RISK, ENVIRONMENTAL FACTORS, AND THE BIOLOGIC CHANGES ASSOCIATED WITH AGING. THE PATHOGENESIS UNDERLYING THE DEVELOPMENT OF VASCULAR AGING, AND VASCULAR CALCIFICATION WITH AGING, IN PARTICULAR, IS STILL NOT FULLY UNDERSTOOD. ACCUMULATING DATA SUGGESTS THAT GENETIC RISK, LIKELY COMPOUNDED BY EPIGENETIC MODIFICATIONS, ENVIRONMENTAL FACTORS, INCLUDING DIABETES AND CHRONIC KIDNEY DISEASE, AND THE PLASTICITY OF VASCULAR SMOOTH MUSCLE CELLS TO ACQUIRE AN OSTEOGENIC PHENOTYPE ARE MAJOR DETERMINANTS OF AGE-ASSOCIATED VASCULAR CALCIFICATION. UNDERSTANDING THE MOLECULAR MECHANISMS UNDERLYING GENETIC AND MODIFIABLE RISK FACTORS IN REGULATING AGE-ASSOCIATED VASCULAR PATHOLOGY MAY INSPIRE STRATEGIES TO PROMOTE HEALTHY VASCULAR AGING. THIS ARTICLE SUMMARIZES CURRENT KNOWLEDGE OF CONCEPTS AND MECHANISMS OF AGE-ASSOCIATED VASCULAR DISEASE, WITH AN EMPHASIS ON VASCULAR CALCIFICATION. 2023 15 5185 35 PREMATURE PHYSIOLOGIC AGING AS A PARADIGM FOR UNDERSTANDING INCREASED RISK OF ADVERSE HEALTH ACROSS THE LIFESPAN OF SURVIVORS OF CHILDHOOD CANCER. THE IMPROVEMENT IN SURVIVAL OF CHILDHOOD CANCER OBSERVED ACROSS THE PAST 50 YEARS HAS RESULTED IN A GROWING ACKNOWLEDGMENT THAT SIMPLY EXTENDING THE LIFESPAN OF SURVIVORS IS NOT ENOUGH. IT IS INCUMBENT ON BOTH THE CANCER RESEARCH AND THE CLINICAL CARE COMMUNITIES TO ALSO IMPROVE THE HEALTH SPAN OF SURVIVORS. IT IS WELL ESTABLISHED THAT AGING ADULT SURVIVORS OF CHILDHOOD CANCER ARE AT INCREASED RISK OF CHRONIC HEALTH CONDITIONS, RELATIVE TO THE GENERAL POPULATION. HOWEVER, AS THE FIRST GENERATION OF SURVIVORS AGE INTO THEIR 50S AND 60S, IT HAS BECOME INCREASINGLY EVIDENT THAT THIS POPULATION IS ALSO AT RISK OF EARLY ONSET OF PHYSIOLOGIC AGING. GERIATRIC MEASURES HAVE UNCOVERED EVIDENCE OF REDUCED STRENGTH AND SPEED AND INCREASED FATIGUE, ALL COMPONENTS OF FRAILTY, AMONG SURVIVORS WITH A MEDIAN AGE OF 33 YEARS, WHICH IS SIMILAR TO ADULTS OLDER THAN 65 YEARS OF AGE IN THE GENERAL POPULATION. FURTHERMORE, FRAILTY IN SURVIVORS INDEPENDENTLY INCREASED THE RISK OF MORBIDITY AND MORTALITY. ALTHOUGH THERE HAS BEEN A PAUCITY OF RESEARCH INVESTIGATING THE UNDERLYING BIOLOGIC MECHANISMS FOR ADVANCED PHYSIOLOGIC AGE IN SURVIVORS, RESULTS FROM GERIATRIC POPULATIONS SUGGEST FIVE BIOLOGICALLY PLAUSIBLE MECHANISMS THAT MAY BE POTENTIATED BY EXPOSURE TO CANCER THERAPIES: INCREASED CELLULAR SENESCENCE, REDUCED TELOMERE LENGTH, EPIGENETIC MODIFICATIONS, SOMATIC MUTATIONS, AND MITOCHONDRIAL DNA INFIDELITY. THERE IS NOW A CRITICAL NEED FOR RESEARCH TO ELUCIDATE THE BIOLOGIC MECHANISMS OF PREMATURE AGING IN SURVIVORS OF CHILDHOOD CANCER. THIS RESEARCH COULD PAVE THE WAY FOR NEW FRONTIERS IN THE PREVENTION OF THESE LIFE-CHANGING OUTCOMES. 2018 16 1385 34 DIABETES IN CHILDHOOD CANCER SURVIVORS: EMERGING CONCEPTS IN PATHOPHYSIOLOGY AND FUTURE DIRECTIONS. WITH ADVANCEMENTS IN CANCER TREATMENT AND SUPPORTIVE CARE, THERE IS A GROWING POPULATION OF CHILDHOOD CANCER SURVIVORS WHO EXPERIENCE A SUBSTANTIAL BURDEN OF COMORBIDITIES RELATED TO HAVING RECEIVED CANCER TREATMENT AT A YOUNG AGE. DESPITE AN OVERALL REDUCTION IN THE INCIDENCE OF MOST CHRONIC HEALTH CONDITIONS IN CHILDHOOD CANCER SURVIVORS OVER THE PAST SEVERAL DECADES, THE CUMULATIVE INCIDENCE OF CERTAIN LATE EFFECTS, IN PARTICULAR DIABETES MELLITUS (DM), HAS INCREASED. THE IMPLICATIONS ARE SIGNIFICANT, BECAUSE DM IS A KEY RISK FACTOR FOR CARDIOVASCULAR DISEASE, A LEADING CAUSE OF PREMATURE DEATH IN CHILDHOOD CANCER SURVIVORS. THE UNDERLYING PATHOPHYSIOLOGY OF DM IN CANCER SURVIVORS IS MULTIFACTORIAL. DM DEVELOPS AT YOUNGER AGES IN SURVIVORS COMPARED TO CONTROLS, WHICH MAY REFLECT AN "ACCELERATED AGING" PHENOTYPE IN THESE INDIVIDUALS. THE TREATMENT-RELATED EXPOSURES (I.E., CHEMOTHERAPY, RADIATION) THAT INCREASE RISK FOR DM IN CHILDHOOD CANCER SURVIVORS MAY BE MORE THAN ADDITIVE WITH ESTABLISHED DM RISK FACTORS (E.G., OLDER AGE, OBESITY, RACE, AND ETHNICITY). EMERGING RESEARCH ALSO POINTS TO PARALLELS IN CELLULAR PROCESSES IMPLICATED IN AGING- AND CANCER TREATMENT-RELATED DM. STILL, THERE REMAINS MARKED INTER-INDIVIDUAL VARIABILITY REGARDING RISK OF DM THAT IS NOT EXPLAINED BY DEMOGRAPHIC AND THERAPEUTIC RISK FACTORS ALONE. RECENT STUDIES HAVE HIGHLIGHTED THE ROLE OF GERMLINE GENETIC RISK FACTORS AND EPIGENETIC MODIFICATIONS THAT ARE ASSOCIATED WITH RISK OF DM IN BOTH THE GENERAL AND ONCOLOGY POPULATIONS. THIS REVIEW SUMMARIZES OUR CURRENT UNDERSTANDING OF RECOGNIZED RISK FACTORS FOR DM IN CHILDHOOD CANCER SURVIVORS TO HELP INFORM TARGETED APPROACHES FOR DISEASE SCREENING, PREVENTION, AND TREATMENT. FURTHERMORE, IT HIGHLIGHTS THE EXISTING SCIENTIFIC GAPS IN UNDERSTANDING THE RELATIVE CONTRIBUTIONS OF INDIVIDUAL THERAPEUTIC EXPOSURES AND THE MECHANISMS BY WHICH THEY EXERT THEIR EFFECTS THAT UNIQUELY PREDISPOSE THIS POPULATION TO DM FOLLOWING CANCER TREATMENT. 2023 17 6030 33 THE BURGEONING CARDIOVASCULAR DISEASE EPIDEMIC IN INDIANS - PERSPECTIVES ON CONTEXTUAL FACTORS AND POTENTIAL SOLUTIONS. CARDIOVASCULAR DISEASES (CVD) ARE THE LEADING CAUSE OF DEATH AND DISABILITY IN INDIA. THE CVD EPIDEMIC IN INDIANS IS CHARACTERIZED BY A HIGHER RELATIVE RISK BURDEN, AN EARLIER AGE OF ONSET, HIGHER CASE FATALITY AND HIGHER PREMATURE DEATHS. FOR DECADES, RESEARCHERS HAVE BEEN TRYING TO UNDERSTAND THE REASON FOR THIS INCREASED BURDEN AND PROPENSITY OF CVD AMONG INDIANS. IT CAN PARTLY BE EXPLAINED BY POPULATION-LEVEL CHANGES AND THE REMAINING BY INCREASED INHERENT BIOLOGICAL RISK. WHILE INCREASED BIOLOGICAL RISK CAN BE ATTRIBUTED TO PHENOTYPIC CHANGES CAUSED BY EARLY LIFE INFLUENCES, SIX MAJOR TRANSITIONS CAN BE CONSIDERED LARGELY RESPONSIBLE FOR THE POPULATION-LEVEL CHANGES IN INDIA-EPIDEMIOLOGICAL, DEMOGRAPHIC, NUTRITIONAL, ENVIRONMENTAL, SOCIAL-CULTURAL AND ECONOMIC. ALTHOUGH CONVENTIONAL RISK FACTORS EXPLAIN SUBSTANTIAL POPULATION ATTRIBUTABLE RISK, THE THRESHOLDS AT WHICH THESE RISK FACTORS OPERATE ARE DIFFERENT AMONG INDIANS COMPARED WITH OTHER POPULATIONS. THEREFORE, ALTERNATE EXPLANATIONS FOR THESE ECOLOGICAL DIFFERENCES HAVE BEEN SOUGHT AND MULTIPLE HYPOTHESES HAVE BEEN PROPOSED OVER THE YEARS. PRENATAL FACTORS THAT INCLUDE MATERNAL AND PATERNAL INFLUENCES ON THE OFFSPRING, AND POSTNATAL FACTORS, RANGING FROM BIRTH THROUGH CHILDHOOD, ADOLESCENCE AND YOUNG ADULTHOOD, AS WELL AS INTER-GENERATIONAL INFLUENCES HAVE BEEN EXPLORED USING THE LIFE COURSE APPROACH TO CHRONIC DISEASE. IN ADDITION TO THIS, RECENT RESEARCH HAS ILLUSTRATED THE IMPORTANCE OF THE ROLE OF INHERENT BIOLOGICAL DIFFERENCES IN LIPID METABOLISM, GLUCOSE METABOLISM, INFLAMMATORY STATES, GENETIC PREDISPOSITIONS AND EPIGENETIC INFLUENCES FOR THE INCREASED RISK. A MULTIFACETED AND HOLISTIC APPROACH TO CVD PREVENTION THAT TAKES INTO CONSIDERATION POPULATION-LEVEL AS WELL AS BIOLOGICAL RISK FACTORS WOULD BE NEEDED TO CONTROL THE BURGEONING CVD EPIDEMIC AMONG INDIANS. 2023 18 1207 35 COVID-19 AND CROSSTALK WITH THE HALLMARKS OF AGING. WITHIN THE PAST SEVERAL DECADES, THE EMERGENCE OF NEW VIRAL DISEASES WITH SEVERE HEALTH COMPLICATIONS AND MORTALITY IS EVIDENCE OF AN AGE-DEPENDENT, COMPROMISED BODILY RESPONSE TO ABRUPT STRESS WITH CONCOMITANTLY REDUCED IMMUNITY. THE NEW SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2, SARS-COV-2, CAUSES CORONAVIRUS DISEASE 2019 (COVID-19). IT HAS INCREASED MORBIDITY AND MORTALITY IN PERSONS WITH UNDERLYING CHRONIC DISEASES AND THOSE WITH A COMPROMISED IMMUNE SYSTEM REGARDLESS OF AGE AND IN OLDER ADULTS WHO ARE MORE LIKELY TO HAVE THESE CONDITIONS. WHILE SARS-COV-2 IS HIGHLY VIRULENT, THERE IS VARIABILITY IN THE SEVERITY OF THE DISEASE AND ITS COMPLICATIONS IN HUMANS. SEVERE PNEUMONIA, ACUTE RESPIRATORY DISTRESS SYNDROME, LUNG FIBROSIS, CARDIOVASCULAR EVENTS, ACUTE KIDNEY INJURY, STROKE, HOSPITALIZATION, AND MORTALITY HAVE BEEN REPORTED THAT RESULT FROM PATHOGEN-HOST INTERACTIONS. HALLMARKS OF AGING, INTERACTING WITH ONE ANOTHER, HAVE BEEN PROPOSED TO INFLUENCE HEALTH SPAN IN OLDER ADULTS, POSSIBLY VIA MECHANISMS REGULATING THE IMMUNE SYSTEM. HERE, WE REVIEW THE POTENTIAL ROLES OF THE HALLMARKS OF AGING, COUPLED WITH HOST-CORONAVIRUS INTERACTIONS. OF THESE HALLMARKS, WE FOCUSED ON THOSE THAT DIRECTLY OR INDIRECTLY INTERACT WITH VIRAL INFECTIONS, INCLUDING IMMUNOSENESCENCE, INFLAMMATION AND INFLAMMASOMES, ADAPTIVE IMMUNOSENESCENCE, GENOMIC INSTABILITY, MITOCHONDRIAL DYSFUNCTION, EPIGENETIC ALTERATIONS, TELOMERE ATTRITION, AND IMPAIRED AUTOPHAGY. THESE HALLMARKS LIKELY CONTRIBUTE TO THE INCREASED PATHOPHYSIOLOGICAL RESPONSES TO SARS-COV-2 AMONG OLDER ADULTS AND MAY PLAY ROLES AS AN ADDITIVE RISK OF ACCELERATED BIOLOGICAL AGING EVEN AFTER RECOVERY. WE ALSO BRIEFLY DISCUSS THE ROLE OF ANTIAGING DRUG CANDIDATES THAT REQUIRE PARAMOUNT ATTENTION IN COVID-19 RESEARCH. 2020 19 6188 24 THE IMPACT OF INSOMNIA ON FRAILTY AND THE HALLMARKS OF AGING. THROUGHOUT THE COURSE OF LIFE, THERE ARE AGE-RELATED CHANGES IN SLEEP. DESPITE THESE NORMAL CHANGES, THERE IS A HIGH PERCENTAGE OF OLDER ADULTS THAT REPORT SLEEP DISSATISFACTION WITH A HIGH PERVASIVENESS OF CHRONIC INSOMNIA, THE MOST COMMON SLEEP DISORDER WORLDWIDE, WITH ITS PREVALENCE BEING EXPECTED TO CONTINUOUSLY INCREASE DUE TO THE GROWING RATES OF AGING AND OBESITY. THIS CAN HAVE DIFFERENT ADVERSE HEALTH OUTCOMES, ESPECIALLY BY PROMOTING BOTH PHYSICAL AND COGNITIVE DECLINE, WHICH ULTIMATELY MAY AGGRAVATE FRAILTY IN OLDER ADULTS. MOREOVER, AGE-RELATED FRAILTY AND SLEEP DYSFUNCTION MAY HAVE A COMMON MECHANISM RELATED TO THE HALLMARKS OF CELLULAR AGING. CELLULAR AGING WAS CATEGORIZED INTO NINE HALLMARKS, SUCH AS DNA DAMAGE, TELOMERE ATTRITION AND EPIGENETIC CHANGES. IN THE CONTEXT OF GERIATRIC AND CHRONIC INSOMNIA RESEARCH, THIS REVIEW AIMS AT DISCUSSING THE CURRENT EVIDENCE FROM BOTH ANIMAL MODELS AND HUMAN COHORTS ADDRESSING THE LINK BETWEEN CHRONIC INSOMNIA, THE HALLMARKS OF AGING AND THEIR IMPACT ON FRAILTY. MOREOVER, THE MOST RECENT RESEARCH ABOUT THE PUTATIVE EFFECT OF INSOMNIA THERAPEUTIC APPROACHES ON HALLMARKS OF AGING WILL BE ALSO HIGHLIGHTED. 2023 20 4080 19 MATERNAL LIFESTYLE INTERVENTIONS: TARGETING PRECONCEPTION HEALTH. ABOUT ONE-THIRD OF WOMEN OF REPRODUCTIVE AGE ARE OBESE, PREDISPOSING BOTH MOTHER AND BABY TO UNFAVOURABLE PREGNANCY OUTCOMES AND INITIATING AN INTERGENERATIONAL CYCLE OF CHRONIC METABOLIC DISORDERS. HERE WE SUMMARISE RECENT RESEARCH ON THE INFLUENCE OF MATERNAL METABOLIC HEALTH ON OFFSPRING SUSCEPTIBILITY TO FUTURE CARDIOMETABOLIC DISEASES. CURRENT PRIMARY LIFESTYLE APPROACHES (I.E., DIET AND EXERCISE INTERVENTIONS) TO HALT THE SUCCESSION OF INHERITED AND EPIGENETIC METABOLIC ABNORMALITIES HAVE MET WITH LIMITED SUCCESS DUE TO LATE IMPLEMENTATION, POOR ADHERENCE, AND/OR GENERIC GUIDELINES. IN OUR OPINION, SUCH INTERVENTIONS MUST COMMENCE PRIOR TO CONCEPTION TO IMPROVE BOTH MATERNAL AND CHILD HEALTH OUTCOMES, WITH NEW APPROACHES URGENTLY NEEDED TO INCREASE ADHERENCE TO PRIMARY LIFESTYLE CHANGES AMONG REPRODUCTIVE-AGE WOMEN. 2020